Abstract CT012: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment for resectable (IB-IIIA) non-small cell lung cancer (NSCLC): Event-free survival (EFS) results from the phase 3 CheckMate 816 trial

Abstract Background: CheckMate 816 (NCT02998528), a randomized phase 3 study of neoadjuvant NIVO + chemo vs chemo for resectable NSCLC, met its first primary endpoint with a statistically significant improvement in pathological complete response (pCR) rate (24% vs 2%; odds ratio 13.94 [99% CI, 3.49-55.75; P < 0.0001]). pCR benefit was consistent across key subgroups, including disease stages, histologies, and PD-L1 expression levels. Notably, neoadjuvant NIVO + chemo did not impede feasibility of surgery nor increase incidence of surgical complications or adverse events (AEs) vs chemo alone. We report results from the first prespecified interim analysis of EFS, the other primary endpoint. Methods: Adults with stage IB (≥ 4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK alterations were randomized to NIVO 360 mg + chemo Q3W or chemo Q3W for 3 cycles (n = 179 each). Primary endpoints were EFS and pCR (both assessed by blinded independent review) in the randomized population. EFS was defined as the length of time from randomization to any disease progression precluding surgery, disease progression or recurrence after surgery, or death due to any cause. An exploratory analysis of EFS by pCR status was conducted. Results: At a median follow-up of 29.5 mo (database lock, October 20, 2021), neoadjuvant NIVO + chemo significantly improved EFS vs chemo in the randomized population (median [95% CI], 31.6 mo [30.2-not reached (NR)] vs 20.8 mo [14.0-26.7]; HR [97.38% CI], 0.63 [0.43-0.91]; P = 0.0052; 2-year EFS rates, 64% vs 45%). EFS results in the subgroups by disease stages, histologies, and PD-L1 expression levels are shown in the Table: In the pooled patient population (NIVO + chemo and chemo arms combined), EFS was improved in patients with pCR compared with those without (median, NR vs 21.1 mo; HR [95% CI], 0.11 [0.04-0.29]). Incidence of grade 3-4 treatment-related (33.5% vs 36.9%) and surgery-related AEs (11.4% vs 14.8%) was similar between the NIVO + chemo and chemo arms, as reported previously. Conclusions: In CheckMate 816, neoadjuvant NIVO + chemo showed a statistically significant and clinically meaningful improvement in EFS vs chemo alone. These results, along with the significant improvement in pCR, support NIVO + chemo as a potential new treatment option for patients with stage IB-IIIA resectable NSCLC. Subgroups Median EFS, mo (95% CI) HR (95% CI) NIVO + chemo Chemo Overall (n = 358) 31.6 (30.2-NR) 20.8 (14.0-26.7) 0.63 (0.43-0.91)a Baseline disease stage IB-II (n = 127) NR (27.8-NR) NR (16.8-NR) 0.87 (0.48-1.56) IIIA (n = 228) 31.6 (26.6-NR) 15.7 (10.8-22.7) 0.54 (0.37-0.80) Tumor histology Squamous (n = 182) 30.6 (20.0-NR) 22.7 (11.5-NR) 0.77 (0.49-1.22) Non-squamous (n = 176) NR (27.8-NR) 19.6 (13.8-26.2) 0.50 (0.32-0.79) PD-L1 expression level < 1% (n = 155) 25.1 (14.6-NR) 18.4 (13.9-26.2) 0.85 (0.54-1.32) ≥ 1% (n = 178) NR (NR-NR) 21.1 (11.5-NR) 0.41 (0.24-0.70) 1-49% (n = 98) NR (27.8-NR) 26.7 (11.5-NR) 0.58 (0.30-1.12) ≥ 50% (n = 80) NR (NR-NR) 19.6 (8.2-NR) 0.24 (0.10-0.61) a97.38% CI reported. Chemo, chemotherapy; CI, confidence interval; EFS, event-free survival; HR, hazard ratio; mo, months; NIVO, nivolumab; NR, not reached; PD-L1, programmed death ligand 1. Citation Format: Nicolas Girard, Jonathan Spicer, Mariano Provencio, Shun Lu, Stephen Broderick, Mark M. Awad, Tetsuya Mitsudomi, Keith Kerr, Julie Brahmer, Scott J. Swanson, Enriqueta Felip, Changli Wang, Gene B. Saylors, Ke-Neng Chen, Fumihiro Tanaka, Moishe Liberman, Cecile Dorange, Javed Mahmood, Junliang Cai, Patrick M. Forde. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment for resectable (IB-IIIA) non-small cell lung cancer (NSCLC): Event-free survival (EFS) results from the phase 3 CheckMate 816 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT012.